Multifactorial hypophosphatemia: a diagnostic challenge involving denosumab, iron infusion, renal tubular acidosis, and gastrointestinal losses.

Hypophosphatemia is a complex electrolyte disturbance with diverse etiologies, including decreased intestinal absorption, increased renal loss, intracellular redistribution, and medication effects. We present a diagnostically challenging case of severe, persistent hypophosphatemia in a 39-yr-old female with a history of renal transplantation, chronic gastrointestinal disease, and osteoporosis. The patient presented with acute abdominal pain, nausea, and constipation and was found to have profound hypophosphatemia (<0.3 mmol/L), hypocalcemia, and hypokalemia. Her recent medical history included administration of i.v. ferric carboxymaltose and denosumab, both known to induce hypophosphatemia via FGF23-mediated renal phosphate wasting and secondary hyperparathyroidism. Additional contributing factors in her case included renal tubular acidosis, tertiary hyperparathyroidism, tacrolimus-induced tubular dysfunction, and significant gastrointestinal losses due to prior bowel resections and acute ileus. Despite aggressive i.v. and oral phosphate supplementation, hypophosphatemia persisted, necessitating prolonged therapy and multiple hospital admissions. Reduction of tacrolimus and correction of acidosis improved phosphate reabsorption, but recurrent episodes highlighted the multifactorial nature of her condition. This case underscores the importance of a systematic, multidisciplinary approach to diagnosing and managing hypophosphatemia, particularly in patients with overlapping risk factors and complex medical histories. Clinicians should maintain a high index of suspicion for delayed and persistent hypophosphatemia in at-risk populations especially following parenteral iron and antiresorptive therapies. Early recognition, regular monitoring, and individualized management are essential to prevent serious complications and improve patient outcomes.